Much of the current effort in cancer therapy is aimed at developing approaches to the immunologic control of cancer. To pursue this goal more effectively, a better understanding of the factors that govern the immune response is required. Our objectives are (1) to investigate the effect of antibody on the humoral immune response of mice to sheep erythrocytes and carrier-hapten systems in vivo and in vitro, and on cell-mediated lymphocyte cytotoxicity, and (2) to define subpopulations of B lymphocytes on the basis of cell-surface and functional characteristics. As to the first objective, we plan to determine whether the suppressive effect of antibody on antibody formation is due to phagocytosis of opsonized antigen by macrophages or to attachment of the Fc-receptors on lymphocytes or to complement, and whether the attachment of complexed antigen to lymphocytes via the Fc-portion of antibody plays a role in the "blocking" of lymphocyte cytotoxicity. Regarding the second objective, we will attempt to distinguish subpopulations of B lymphocytes on the basis of function, location in different lymphoid organs, and surface markers, and to investigate signals which cause one type of B cell to differentiate into another. Methods used will include the Mishell-Dutton culture system for measuring the production of antibody in vitro, the 3H-proline assay for lymphocyte cytotoxicity, and column separation of cell populations.